1. Field of the Invention
The present invention is generally related to the modulation of transcription. More specifically, the present invention is related to the regulation of genes controlled by G+C-rich promoters.
2. Description of Related Art
Promoters that govern the transcription of mammalian genes by RNA polymerase II fall broadly into three types: the classical TATAAA-box-dependent promoters, the initiator element (Inr)-dependent promoters, and the G+C-rich promoters which also have been referred to as CpG islands. Transcription initiation at the TATAAA-box-dependent promoters is dictated by the direct interaction of the TATAAA-box with the TATA-binding protein TBP as a first and rate-limiting step (reviewed by Buratowski et al., 1989). Likewise, transcription initiation at Inr-dependent promoters occurs when the Inr element interacts with sequence-specific Inr-binding proteins (Smale & Baltimore, 1989, Smale et al., 1990). The mechanism by which transcription initiation sites within G+C-rich promoters are recognized by the RNA Polymerase II transcription machinery is currently unelucidated.
Transcription initiation of a large number of mammalian genes, including most housekeeping genes, and many highly regulated genes controlling cell growth and differentiation, is under the control of G+C-rich promoters (Rauth et al., 1989). This class of promoter is not found in either the drosophila or yeast genomes. Because a common characteristic of this type of promoter is the presence of a non-canonical TATAAA box and one or more Sp1 binding sites upstream of the major transcription initiation site, several reports have claimed that those sequences are the key functional elements in G+C-rich promoters (Blake et al., 1990, Innis et al., 1991). However, reports that challenged these claims, in some cases even with respect to the same promoter, also have been published (Means & Farnham, 1990a, 1990b, Ackerman et al., 1993). The lack of obvious conserved sequence motifs shared among different G+C-rich promoters, with the exception of the Sp1 binding sites and the “non-canonical” TATAAA boxes, provides further impetus for investigations to elucidate how transcription can initiate non-randomly at these precise genome locations.